Publications

Abstract

Since the beginning of the Coronavirus disease (COVID)-19 pandemic in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for more than 600 million infections and 6.5 million deaths worldwide. Given the persistence of SARS-CoV-2 and its ability to develop new variants, the implementation of an effective and long-term herd immunity appears to be crucial to overcome the pandemic. While a vast field of research has focused on the role of humoral immunity against SARS-CoV-2, a growing body of evidence suggest that antibodies alone only confer a partial protection against infection of reinfection which could be of high importance regarding the strategic development goals (SDG) of the United Nations (UN) and in particular UN SDG3 that aims towards the realization of good health and well being on a global scale in the context of the COVID-19 pandemic.In this review, we highlight the role of humoral immunity in the host defense against SARS-CoV-2, with a focus on highly neutralizing antibodies. We summarize the results of the main clinical trials leading to an overall disappointing efficacy of convalescent plasma therapy, variable results of monoclonal neutralizing antibodies in patients with COVID-19 but outstanding results for the mRNA based vaccines against SARS-CoV-2. Finally, we advocate that beyond antibody responses, the development of a robust cellular immunity against SARS-CoV-2 after infection or vaccination is of utmost importance for promoting immune memory and limiting disease severity, especially in case of (re)-infection by variant viruses.

Abstract

Since the beginning of the Coronavirus disease (COVID)-19 pandemic in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for more than 600 million infections and 6.5 million deaths worldwide. Given the persistence of SARS-CoV-2 and its ability to develop new variants, the implementation of an effective and long-term herd immunity appears to be crucial to overcome the pandemic. While a vast field of research has focused on the role of humoral immunity against SARS-CoV-2, a growing body of evidence suggest that antibodies alone only confer a partial protection against infection of reinfection which could be of high importance regarding the strategic development goals (SDG) of the United Nations (UN) and in particular UN SDG3 that aims towards the realization of good health and well being on a global scale in the context of the COVID-19 pandemic.In this review, we highlight the role of humoral immunity in the host defense against SARS-CoV-2, with a focus on highly neutralizing antibodies. We summarize the results of the main clinical trials leading to an overall disappointing efficacy of convalescent plasma therapy, variable results of monoclonal neutralizing antibodies in patients with COVID-19 but outstanding results for the mRNA based vaccines against SARS-CoV-2. Finally, we advocate that beyond antibody responses, the development of a robust cellular immunity against SARS-CoV-2 after infection or vaccination is of utmost importance for promoting immune memory and limiting disease severity, especially in case of (re)-infection by variant viruses.

Abstract

Objective: To report results of the 2021 French National Perinatal Survey (ENP) in metropolitan France and assess trends in the main indicators of perinatal health, medical practices, and risk factors in France since 1995.

Population and method: All the samples included all women giving birth at a gestational age of at least 22 weeks of gestation and/or to an infant weighing at least 500 grams in all maternity units in metropolitan France during one week in 1995 (N=13 048), 2003 (N=14 324), 2010 (N=14 546), 2016 (N=12 553), and 2021 (N=12 088). The data came from postpartum interviews of the women at the hospital and their medical records. Comparisons between surveys showed trends over time.

Results: Between 1995 and 2021, maternal characteristics changed. Maternal age and the frequency of women with obesity rose: in 2021, 24.6% of women were 35 years or older (21.1% in 2016, 19.2% in 2010, 15.9% in 2003 and 12.4% in 1995) and 14.4% were obese (11.8% in 2016, 9.9% in 2010 and 7.4% in 2003). Some antenatal prevention behaviors that improved in 2021 were not smoking during the third trimester, acid folic administration before pregnancy, and vaccination against influenza. The percentage of women with an early prenatal appointment (« 4^th month appointment »), implemented to facilitate screening of maternal vulnerability during pregnancy, has continued to rise. The percentage of women receiving prenatal care by midwives has risen markedly (39.0% in 2021 versus 11.7% in 2016). Serum screening for Down syndrome continues to increase (91.8% of women in 2021). The rate of induction of labor has risen significantly (20.2% in 1995 and 25.8% in 2021). The mode of delivery has not varied significantly since 2003; in 2021, the cesarean rate was 21.4% and the instrumental vaginal delivery rate 12.4%. Episiotomy was increasingly rare, among both primiparous and multiparous women (16.5% and 2.9% in 2021, respectively). The prevalence of coronavirus (SARS-CoV2) infection during pregnancy was 5.7%. Preterm live births increased regularly, slightly but significantly over the 1995-2016 period and then remained stable between 2016 and 2021 (7.0%). In 2021, 56.3% of women exclusively breastfed during their hospital stay, a modest increase in comparison with 2016 (54.6%).

Conclusion: Routine national perinatal surveys highlight positive trends over time in some preventive practices, decreases in some medical interventions consistent with national guidelines, and the increasing role of midwives in prenatal care. Nonetheless, some indicators remain less than optimal and require more detailed analyses.

Abstract

Background: To evaluate the association between exposure to early skin-to-skin contact (SSC) and incidence of late-onset sepsis (LOS) in extremely and very preterm infants.

Methods: Observational study using the national population-based EPIPAGE-2 cohort in 2011. A propensity score for SSC exposure was used to match infants with and without exposure to SSC before day 4 of life and binomial log regression used to estimate risk ratios and CIs in the matched cohort. The primary outcome was at least one episode of LOS during hospitalization. Secondary outcomes were the occurrence of any late-onset neonatal infection (LONI), LOS with Staphylococcus or Staphylococcus aureus, incidence of LOS and LONI per 1000 central venous catheter days.

Results: Among the 3422 included infants, 919 were exposed to early SSC. The risk ratio (RR) for LOS was 0.86 (95% CI, 0.67-1.10), for LONI was 1.00 (95% CI, 0.83-1.21), and for LOS with Coagulase-negative Staphylococcus or Staphylococcus aureus infection was 0.91 (95% CI, 0.68-1.21) and 0.77 (95% CI, 0.31-1.87). The incidence RR for LOS per-catheter day was 0.87 (95% CI, 0.64-1.18).

Conclusion: Early SSC exposure was not associated with LOS or LONI risk. Thus, their prevention should not be a barrier to a wider use of SSC.

Impact: Kangaroo Mother Care decreased neonatal infection rates in middle-income countries. Skin-to-skin contact is beneficial for vulnerable preterm infants but barriers exist to its implementation. In a large population-based study using a propensity score methods, we found that skin-to-skin contact before day 4 of life was not associated with a decreased risk of late-onset-sepsis in very and extremely preterm infants. Early skin-to-skin contact was not associated with an increased risk of any late-onset-neonatal-infection, in particular with staphylococcus. The fear of neonatal infection should not be a barrier to a wider use of early skin-to-skin contact in this population.

Abstract

Objective: To identify risk factors for moderate or severe hypoxic-ischemic encephalopathy (HIE), or neonatal death in clinical placental abruption.

Material and methods: A nested case-control study within a cohort of singleton pregnancies complicated by placental abruption with a live born infant at two academic reference centers in France, from 2006 to 2019. Cases were patients who gave birth to an infant with moderate or severe HIE or death within 28 days (HIE/death group), and controls were patients whose infant did not have any of these outcomes (no-HIE group). Independent risk factors were identified by logistic regression. Binary decision tree discriminant (CART) analysis was performed to define high-risk subgroups of HIE or death.

Results: Among 152 patients, the infants of 44 (29%) had HIE or death. Out-of-hospital placental abruption and fetal bradycardia at admission were more frequent in cases than in controls: 39 (89%) vs 61 (56%), p < .01 and 24 (59%) vs 19 (18%), p < .01, respectively. In multivariate analysis, out-of-hospital placental abruption (aOR, 7.05; 95% CI, 1.94-25.66) and bradycardia at admission (aOR, 8.60; 95% CI, 2.51-29.42) were independently associated with an increased risk of HIE or death. The combination of out-of-hospital placental abruption and bradycardia was the highest risk situation associated with HIE or death (67%). The decision-to-delivery interval was 15 [12-20] minutes among cases.

Conclusion: Out-of-hospital placental abruption combined with bradycardia at admission was associated with a major risk of moderate or severe HIE or death. An optimal decision-to-delivery interval does not guarantee the absence of an adverse neonatal outcome.

Abstract

To develop a new tool to assess the global quality of care for post-partum hemorrhage (PPH)-the leading preventable cause of maternal mortality worldwide-and to identify characteristics of maternity units associated with inadequate PPH management. This is a secondary analysis of the EPIMOMS population-based study conducted in 2012-2013 in 119 french maternity units (182,309 women who gave birth). We included women with severe PPH. We first developed a score to quantify the quality of care for PPH. Then, we identified characteristics of the maternity units associated with « inadequate care » defined by a score below the 25th percentile, with multi-level logistic regression adjusted for individual characteristics. The score combined 8 key components of care and took into account delivery mode and PPH cause. For PPH after vaginal delivery, the risk of inadequate care was increased in low versus high-volume maternity units (< 1000 deliveries/year: aOR-2.20 [1.12-4.32], [1000-2000 [deliveries/year: aOR-1.90 [1.02-3.56] compared to ≥ 3500 deliveries/year), in private versus public units (aOR-1.72 [1.00-2.97]), and in low versus high-level of care units (aOR-2.04 [1.24-3.35]). For PPH after cesarean, the only characteristic associated with an increased risk of inadequate care was the absence of 24/24-onsite anesthesiologist (aOR-4.34 [1.41-13.31]). These results indicate where opportunities for improvement are the greatest.

Abstract

he objective of this study was to determine the relationship between maternal pre-pregnancy body mass index (BMI) and child hyperactivity-inattention symptoms (HIS) at 5 years, including preterm and term-born children, and to determine whether this association varied with gestational age. Maternal pre-pregnancy BMI and offspring HIS were assessed in 10,898 participants born ≥ 33 weeks of gestation from the ELFE cohort and 2646 children born between 23 and 34 weeks from the EPIPAGE 2 cohort. Reported pre-pregnancy weight (kg) and measured height (m) were collected from mothers at inclusion and used to classify BMI (kg/m²). Child HIS were evaluated using the Strengths and Difficulties Questionnaire around 5 years of age. Logistic regression estimated odds ratios (OR) of a high HIS score (≥ 90th percentile) in the ELFE cohort and generalized estimated equations were used in EPIPAGE 2 to account for non-independence of multiple births. As a negative control, paternal BMI was also considered as an exposure of interest in sensitivity analyses. Maternal pre-pregnancy obesity and overweight were associated with child HIS at 5 years in ELFE (adjusted OR [aOR] for obesity 1.27 [1.06, 1.53]; overweight aOR 1.16 [1.00, 1.36]) and pre-pregnancy obesity was associated with high HIS scores in preterm infants of EPIPAGE 2 (aOR 1.48 [1.06, 2.08]). In ELFE, the magnitude of the association increased with decreasing gestational age (interaction p = 0.02). High maternal pre-pregnancy BMI is associated with greater likelihood of high HIS scores in both at-term and preterm children at 5 years of age.

Abstract

Objective: To re-visit short-term outcomes and associated risk factors of newborns with hypoxic-ischemic encephalopathy (HIE) in an era where hypothermia treatment (HT) is widespread.

Methods: This is a prospective population-based cohort in French neonatal intensive care units (NICU). Neonates born at or after 34 weeks of gestational age with HIE were included; main outcomes were in-hospital death and discharge with abnormal or normal MRI. Associations of early perinatal risk factors, present at birth or at admission to NICU, with these outcomes were studied.

Results: A total of 794 newborns were included and HT was administered to 670 (84.4%); 18.3% died and 28.5% and 53.2% survived with abnormal and normal MRI, respectively. Severe neurological status, Apgar score at 5 mn ≤5, lactate at birth ≥11 mMoles/l, and glycemia ≥100 mg/dL at admission were associated with an increased risk of death (relative risk ratios (aRRR) (95% CI) 19.93 (10.00-39.70), 2.89 (1.22-1.62), 3.06 (1.60-5.83), and 2.55 (1.38-4.71), respectively). Neurological status only was associated with survival with abnormal MRI (aRRR (95% CI) 1.76 (1.15-2.68)).

Conclusion: Despite high use of HT in this cohort, 46.8% died or presented brain lesions. Early neurological and biological examinations were associated with unfavorable outcomes and these criteria could be used to target children who warrant further neuroprotective treatment.

Trial registration: Clinical trial registry, NCT02676063, ClinicalTrials.gov.

Impact: In this population-based cohort of newborns with HIE where 84% received hypothermia, 46.8% still had an unfavorable evolution (death or survival with abnormal MRI). Risk factors for death were high lactate, low Apgar score, severe early neurological examination, and high glycaemia. While studies have established risk factors for HIE, few have focused on early perinatal factors associated with short-term prognosis. This French population-based cohort updates knowledge about early risk factors for adverse outcomes in the era of widespread cooling. In the future, criteria associated with an unfavorable evolution could be used to target children who would benefit from another neuroprotective strategy with hypothermia.

Abstract

Background: Cardiovascular diseases, including acute coronary syndromes, are the leading cause of maternal death in many developed countries.

Objective: We assessed acute coronary syndrome incidences during pregnancy, peripartum, and postpartum periods. We also compared overall pregnancy (ie, covering all 3 periods) incidence with that found in nonpregnant women of childbearing age.

Study design: All women aged between 15 and 49 years without ischemic heart disease who delivered between 2010 and 2018 in France were included in the CONCEPTION cohort. Data were extracted from the French National Health Insurance Information System database. Acute coronary syndromes were defined according to the International Classification of Diseases, Tenth Revision codes recorded in the principal hospital diagnosis. We used Poisson regression to estimate crude acute coronary syndrome incidences, and tested age-adjusted Poisson models to compare the incidence risk ratio of acute coronary syndrome between pregnant and nonpregnant women, with 95% confidence intervals.

Results: Among 6,298,967 deliveries in France, we observed 225 first-time acute coronary syndrome diagnoses during overall pregnancy (overall pregnancy-related acute coronary syndrome incidence, 4.34/100,000 person-years; 1 case/23,000 pregnancies). In multivariate analysis, independent factors associated with acute coronary syndrome were age, social deprivation, obesity, tobacco use, chronic hypertension, and hypertensive disorders of pregnancy (all P<.05). Among the nonpregnant women aged 15 to 49 years in the general French population, 18,247 cases of acute coronary syndrome (incidence, 16.5/100,000 person-years) occurred throughout the whole study period (>100 million person-years). Compared with the acute coronary syndrome incidence in nonpregnant women, age-adjusted overall pregnancy-related acute coronary syndrome incidence was lower (incidence rate ratio, 0.76; 95% confidence interval, 0.57-0.98; P<.05). Although compared with nonpregnant women, age-adjusted incidence rates were lower during pregnancy, risk was increased during peripartum and postpartum periods.

Conclusion: With an incidence of 4.34 per 100,000 person-years, acute coronary syndrome still accounts for a significant proportion of maternal mortality. The peripartum and postpartum periods remain high-risk periods, and greater efforts should be made in terms of acute coronary syndrome prevention, especially because several cardiovascular risk factors are treatable, such as tobacco use and hypertensive disorders of pregnancy.

Abstract

Background: In early terminations of pregnancy for fetal anomaly (TOPFA) without identified cytogenetic abnormality, a fetal autopsy is recommended for diagnostic purposes, to guide genetic counseling. Medical induction, which allows analysis of a complete fetus, is generally preferred over surgical vacuum aspiration. Our objective was to assess the diagnostic value of fetal autopsies in these early terminations, relative to the first-trimester ultrasound, overall and by termination method.

Materials: For this retrospective study at the Port Royal Maternity Hospital, we identified all TOPFA performed from 11 weeks to 16 weeks diagnosed at the first-trimester ultrasound in cases with a normal karyotype. The principal endpoint was the additional value of the autopsy over /compared to the ultrasound and its impact on genetic counseling, globally and by termination method. The secondary objective was to compare the complication rate by method of termination.

Results: The study included 79 women during period of 2013-2017: 42 with terminations by medical induction and 37 by aspiration. Fetal autopsy found additional abnormalities in 54.4% of cases, more frequently after medical induction (77.5%) than after aspiration (21.4%, p < .01). Genetic counseling was modified in 20.6% of cases, more often after induction (32.5% vs 3.6%, p < .01). The length of stay was significantly longer and a secondary aspiration was required in 16,7% of case in the medical induction group (p < .01).

Conclusion: Medically induced vaginal expulsion appears preferable and can change genetic counseling for subsequent pregnancies.